Abstract

Obesity is reaching epidemic proportions worldwide with profound impact on health resulting in reduced quality of life, early death. Deposition of excess fatty acids (FAs) into fat cells in the form of triglycerides (TGs) is the biochemical basis of obesity, thus any imbalance in food intake and energy utilization may result in obesity. This homeostasis is complex and is regulated by a host of metabolic and endocrine factors which are poorly understood. Obesity contributes to pathologies, such as the metabolic syndrome (MetS), cardiovascular disease (CVD), type 2 diabetes mellitus (T2DM), hypertension, endothelial dysfunction [ED] and testosterone deficiency (hypogonadism). An increases in the prevalence of overweight (body mass index (BMI) 25-29.9 kg m−2) and obesity (BMI ≥ 30 kg m−2) in adult men by more than 25% in the last 8 years according to WHO estimates. Overweight and moderate obesity is predominantly associated with reductions in total testosterone; whereas, free testosterone levels remain within the reference range, especially in younger men. Reductions in total testosterone levels are largely a consequence of reductions in sex hormone binding globulin (SHBG) due to obesity-associated hyperinsulinemia. Glucagon-like peptide-1 receptor agonists (GLP-1 RA) are used for weight loss and insulin dose reduction in obese insulin-using type 2 diabetic patients. A plausible mechanism by which GLP-1 RA may induce weight loss is by suppressing appetite signalling in the brain and increasing satiety, leading to a reduced food intake [9, 10]. GLP-1 receptors are present in the central nervous system suggesting direct actions of GLP-1 in the brain [11]. GLP-1 infusions can enhance satiety and reduce energy intake in type 2 diabetes patients [12]. Furthermore, GLP-1 RA attenuates binge eating in obese patients [13], suggesting a role of GLP-1 RA in certain eating types. A recent systematic review and meta-analysis including 2.8 million people and 270 000 deaths reported increased overall mortality only in those with extreme obesity (BMI > 35 kg m−2, hazard ratio (HR) 1.29, 95% confidence interval (CI) 1.18-1.41), but not in grade 1 obesity (BMI